Parkinson's disease (PD) results from the progressive loss of dopamine (DA) neurons in the midbrain. Replacement of the lost DA neurons with fetal midbrain cells through neural transplantation in clinical trials has produced clinical benefits and has laid a foundation for cell therapy in PD. This therapy, however, is hindered by the limited supply of effective donor cells. Human embryonic stem (hES) cells (NIH Registry WA01 and WA09), established from the inner cell mass of a preimplantation embryo, are capable of almost unlimited proliferation in an undifferentiated state, yet retain the potential to differentiate into almost all cell and tissue types of the body including DA neurons. Thus ES cells may provide a simple and continual source of specialized human cells, which can be standardized and banked. This application is to resolve a single but crucial issue surrounding potential stem cell replacement therapy for PD, i.e., which hES-derived cell type, neuroepithelial cells, DA neuron progenitors, or DA neurons, is best for transplant therapy in PD. This study is based on our success in guiding hES cells to neuroepithelial cells, DA neuron progenitors and mature DA neurons in culture. The criteria for determining the candidate cell type include safety to recipients, efficacy of the cells for functional replacement, efficiency in cell production, and simplicity for standardization of cell preparation procedures. The proposed study will determine the ideal hES-derived cells for PD therapy, thus leading to preclinical studies to transplant the selected cells into a monkey PD model we have established, and to bank and/or standardize the cell production in our Biomanufacturing Facility before clinical trials.